MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells. Issue 12 (December 2020)

• Record Type: Journal Article
• Authors: Mendonça, Daniela Baccelli; Nguyen, Joe Truong; Haidar, Fatima; Fox, Alexandra Lucienne; Ray, Connor; Amatullah, Halimah; Liu, Fei; Kim, Jin Koo; Krebsbach, Paul H.
• Is Part Of: Heliyon. Volume 6:Issue 12(2020)
• Publication Date: 2020-12
• Subjects: MicroRNA-1911-3p -- mEAK-7 -- mTOR signaling -- Lung cancer -- Cell proliferation -- Cell migration -- Cell biology -- Gene expression -- Gene regulation -- Cancer research -- Oncology; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2020.e05734
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: Regulation of mTOR signaling depends on an intricate interplay of post-translational protein modification. Recently, mEAK-7 (mTOR associated protein, eak-7 homolog) was identified as a positive activator of mTOR signaling via an alternative mTOR complex. However, the upstream regulation of mEAK-7 in human cells is not known. Because microRNAs are capable of modulating protein translation of RNA in eukaryotes, we conducted a bioinformatic search for relevant mEAK-7 targeting microRNAs using the Exiqon miRSearch V3.0 algorithm. Based on the score obtained through miRSearch V3.0, the top predicted miRNA (miR-1911-3p) was studied. miR-1911-3p mimics decreased protein levels of both mEAK-7 and mTORC1 downstream effectors p-S6 and p-4E-BP1 in non-small cell lung carcinoma (NSCLC) cell lines H1975 and H1299. miR-1911-3p levels and MEAK7 mRNA/mEAK-7/mTOR signaling levels were negatively correlated between normal lung and NSCLC cells. miR-1911-3p directly interacted with MEAK7 mRNA at the 3′-UTR to negatively regulate mEAK-7 and significantly decreased mTOR localization to the lysosome. Furthermore, miR-1911-3p significantly decreased cell proliferation and migration in both H1975 and H1299 cells. Thus, miR-1911-3p functions as a suppressor of mTOR signaling through the regulation of MEAK7 mRNA translation in human cancer cells. Abstract : MicroRNA-1911-3p; mEAK-7; mTOR signaling; Lung cancer; Cell proliferation; Cell migration; Cell biology; Gene expression; Gene regulation; Cancer research; Oncology.